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• W2922205921 abstract "Introduction: Hereditary alpha tryptasemia (HaT) is a recently described autosomal dominant condition caused by increased TPSAB1 copy number, resulting in over-expression of alpha-tryptase (Lyons et al. Nat. Genet. 2016 Dec;48(12): 1564-1569.). It is reported to affect 3-5% of the general population and is associated with a variety of gastrointestinal (GI) complaints including GI dismotility, inflammation, abdominal pain and GERD. Methods: The mast cell (MC) of these patients were further characterized by examining the lamina propria mononuclear cells (LPMC) isolated from ileal biopsies of HaT, Crohn's disease (CD) and systemic mastocytosis (SM) patients by CyTOF. To elevate this characterization further, we examined expression patterns of these markers in the duodenum of HaT patients compared with IBS patients by immunohistochemistry (IHC). Since exosomes reflect the composition of cell membranes in tissue, we also evaluated urinary exosomes in these patients. Results: Our 22-patient cohort with a confirmed HaT diagnosis had a mean basal serum tryptase of 15.4 and a mean MC number per high powered field (hpf) of 50.6 in small bowel histopathology sections. Non-HaT patients have < 8.5 μg/L tryptase and < 20/hpf MC (the MC/hpf number is debated: Gastro-enterol. Hepatol. (NY) 2010 Dec; 6(12): 772-777). Defining MC by CD117+ and FceR1+, we found that MCs were increased in HaT patients compared with patients with quiescent CD. Furthermore, MC from HaT patients expressed HLA-DR (MHC Class II antigen). Additionally, CyTOF data revealed T-helper (Th) lymphocytes (CD4+ T-cells) with CXCR5 in HaT LPMC compared with CD4+ T-cells form CD and SM. In HaT patient sections, there were elevated numbers of CD117+FceR1+ cells with HLA-DR compared with the IBS patient sections where a paucity of cells with these characteristics were observed. We noted that the exosome lipidomics were consistent with a MC signature. Flow cytometry revealed that a portion of the HaT exosomes had an MC marker, CD117+. Proteomics data revealed that multiple pathways, including mTOR and protease-activated receptor 1 (PAR1), were elevated. CyTOF data on LPMC confirmed an increase in phosphorylated S6, which is downstream from mTOR, in HaT patients compared with CD patients. Conclusion: Taken together, the data suggest that MC could be potentially acting as antigen presenting cells (APC) in HaT patients." @default.
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• W2922205921 date "2018-10-01" @default.
• W2922205921 modified "2023-09-23" @default.
• W2922205921 title "CD117+ Exosomes and Mast Cells From Hereditary Alpha Tryptasemia Patients Reveal Unique Phosphorylation, Lipidomics, and Proteomics Profiles: Category Award (Small Intestine): Presidential Poster Award" @default.
• W2922205921 doi "https://doi.org/10.14309/00000434-201810001-01173" @default.
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